We have reported the identification of a protein phosphatase that interacts with the phosphorylated form of RLK5, a receptor-like protein kinase from Arabidopsis thaliana. RLK5 has features characteristic of the growth factor receptor kinases, including an extracellular domain of tandem leucine-rich repeats, a transmembrane domain, and a C-terminal serine/threonine protein kinase catalytic domain. Numerous serine/threonine receptor kinases have been identified in higher eukaryotes including the TGF-b/activin receptor superfamily in animals and the receptor-like kinases from higher plants. However, the mechanisms by which these receptors transduce a signal is unknown. Interaction cloning was used to identify an Arabidopsis protein, termed KAPP for kinase associated protein phosphatase, associates with the catalytic domain of RLK5 and consists of three functional domains: an N-terminal type one signal anchor, a central kinase interaction (KI) domain responsible for interaction with RLK5, and a C-terminal region with homology with type 2C serine/threonine protein phosphatases. KI domain association requires phosphorylation of RLK5 as shown by in vitro binding assays. Interaction of a protein with the phosphorylated form of a receptor protein kinase is reminiscent of the interaction of SH2 domain-containing proteins with tyrosine kinases. Interaction of the KI domain of KAPP with phosphorylated RLK5 suggests that this may be a general mechanism for receptor protein kinase-mediated cellular signaling common to both receptor tyrosine and receptor serine/threonine protein kinases. The autophosphorylation sites in the catalytic domain of RLK5 are being mapped with MALDI-MS.